title: Profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets using gastrointestinal simulation technology.
abstract: The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption. Gastrointestinal simulation technology (GST) was used to simulate the in vivo plasma concentration-time curve and was implemented by GastroPlus™ software. Lansoprazole, a typical BCS class II drug, was chosen as a model drug. Firstly, physicochemical and pharmacokinetic parameters of lansoprazole were determined or collected from literature to construct the model. Validation of the developed model was performed by comparison of the predicted and the experimental plasma concentration data. We found that the predicted curve was in a good agreement with the experimental data. Then, parameter sensitivity analysis (PSA) was performed to find the key parameters of oral absorption. The absorption was particularly sensitive to dose, solubility and particle size for lansoprazole enteric-coated tablets. With a single dose of 30 mg and the solubility of 0.04 mg/ml, the absorption was complete. A good absorption could be achieved with lansoprazole particle radius down to about 25 μm. In summary, GST is a useful tool for profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets and guiding the formulation optimization.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Wu
authors.forename: Le
authors.initials: L
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.forename: Congcong
authors.initials: C
authors.lastname: Ren
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ai
authors.forename: He
authors.initials: H
authors.lastname: Lian
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000042:Absorption; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D003198:Computer Simulation; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D064747:Lansoprazole / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D010316:Particle Size; D054328:Proton Pump Inhibitors / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013608:Tablets, Enteric-Coated; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D013608:Tablets, Enteric-Coated; D064747:Lansoprazole
keywords: Formulation optimization; GastroPlus™; Gastrointestinal simulation technology; Lansoprazole; Parameter sensitivity analysis